Drug shortages in the United States have become an increasing problem. Taxol®, otherwise known by the generic name paclitaxel, is a chemotherapeutic agent used to treat breast cancer, as well as ovarian, lung and colon cancers. Shortages of paclitaxel can limit or curtail treatment options for cancer patients. New, more efficient procedures for making paclitaxel may avoid such drug shortages and ensure a reliable pharmaceutical supply chain.
Paclitaxel has been produced by semisynthetic and plant cell fermentation (PCF) techniques. The semisynthetic method of making paclitaxel (shown below) requires over seventeen synthetic steps and involves use of voluminous organic solvents during the production process.
While the simplicity of coupling the necessary phenylisoserine side chain to the diterpene core of the paclitaxel molecule made such semisynthetic methods attractive, the multiple steps and the environmental hazards of the solvents and side products involved make the semisynthetic approach less attractive than the plant cell fermentation methods.
However, while the plant cell fermentation procedures do tend to use less toxic materials, the amount of paclitaxel obtained can be low. For example, in cell cultures, the concentration of paclitaxel ranges from 0.04 to 0.2%, depending on cell lines. Large fermentation vats must be used and the isolation and separation of paclitaxel from the milieu of plant cell lysates must be very efficient to obtain useful amounts of paclitaxel.